Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne muscular dystrophy, Exon Skipping, DMD, Exon 53, Exon 45, Ambulatory, Pediatric, Duchenne
Brief summary
The main objective of this study is to evaluate the efficacy of SRP-4045 (casimersen) and SRP-4053 (golodirsen) compared to placebo in participants with DMD with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.
Detailed description
This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible participants with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 milligrams/kilograms (mg/kg) SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open-label extension period in which all participants will receive open-label active treatment for 48 weeks (up to Week 144 of study). The study will enroll approximately 222 participants. Twice as many participants will be randomized to receive active treatment as will receive placebo (2:1 randomization). Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests, such as the 6-minute walk test (6MWT). All participants will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96. Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study. Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.
Interventions
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1 is double-blind and randomized; Part 2 is open-label.
Eligibility
Sex/Gender
MALE
Age
6 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
* Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping * Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight). * Intact right and left biceps brachii muscles or 2 alternative upper arm muscle groups * Mean 6MWT ≥300 meters and ≤450 meters * Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted
Exclusion criteria
* Treatment with gene therapy at any time * Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with PRO045 (BMN 045), PRO053 (BMN 053), or PRO051 (BMN 051) within 24 weeks prior to Week 1 * Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1 * Major surgery within 3 months prior to Week 1 * Presence of other clinically significant illness * Other inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in the 4-Step Ascend Velocity at Week 96 | Baseline, Week 96 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in the Total Distance Walked During 6MWT at Week 96 | Baseline, Week 96 | — |
| Change from Baseline in Rise from Floor Velocity at Week 96 | Baseline, Week 96 | — |
| Change From Baseline in the 4-Step Ascend Velocity at Week 144 | Baseline, Week 144 | — |
| Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 | Baseline, Week 48 or Week 96 | — |
| Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96 | Baseline, Week 96 | The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, participants will be asked to perform 17 different functional activities, including a 10 meter walk/run, rising from a sit to standing, standing on 1 leg, climbing a box step, descending a box step, rising from lying to sitting, rising from the floor, lifting the head, standing on heels, and jumping. Participants will be graded as follows: 2 = achieves goal without any assistance; 1 = modified method but achieves goal independent of physical assistance from another person; and 0 = unable to achieve goal independently. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function. |
| Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96 | Baseline, Week 48 or Week 96 | — |
| Change From Baseline in Total Distance Walked During the 10-meter walk/run (10-MWR) Velocity | Baseline, Week 96 | — |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Mexico, Poland, Russia, Serbia, South Korea, Spain, Sweden, United Kingdom, United States
Outcome results
None listed